Human epidermal growth factor receptor 2 (HER2) mutations play a role as a driver gene in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC harboring HER2 mutations exhibit poor responses to conventional chemotherapy and immunotherapy, hence targeted therapies against HER2 are under extensive investigation. This review analyzes the biological characteristics of HER2, an overview of clinical trials for targeted therapy drugs, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate, and research directions for drug resistance in NSCLC. Currently, Pyrotinib and Trastuzumab deruxtecan have been approved for the treatment of advanced NSCLC with HER2 mutations, suitable for patients who have failed standard therapy, which is far from meeting the clinical demands. Novel selective HER2 TKIs are gradually emerging. Future exploration trends are gradually shifting from single drugs to combination strategies, and are exploring more precise selection strategies as well as research on resistance mechanisms. These studies will provide a theoretical basis for clinical treatment strategies for advanced NSCLC with HER2 mutations, promoting the development of personalized therapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Receptor, ErbB-2/metabolism* ; Mutation ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use* ; Antineoplastic Agents/therapeutic use*

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

OBJECTIVES: We propose a novel deep learning segmentation algorithm (DSRF) based on multi-scale supervision and residual feedback strategy for precise segmentation of the optic chiasm and optic nerves in CT images of nasopharyngeal carcinoma (NPC) patients. METHODS: We collected 212 NPC CT images and their ground truth labels from SegRap2023, StructSeg2019 and HaN-Seg2023 datasets. Based on a hybrid pooling strategy, we designed a decoder (HPS) to reduce small organ feature loss during pooling in convolutional neural networks. This decoder uses adaptive and average pooling to refine high-level semantic features, which are integrated with primary semantic features to enable network learning of finer feature details. We employed multi-scale deep supervision layers to learn rich multi-scale and multi-level semantic features under deep supervision, thereby enhancing boundary identification of the optic chiasm and optic nerves. A residual feedback module that enables multiple iterations of the network was designed for contrast enhancement of the optic chiasm and optic nerves in CT images by utilizing information from fuzzy boundaries and easily confused regions to iteratively refine segmentation results under supervision. The entire segmentation framework was optimized with the loss from each iteration to enhance segmentation accuracy and boundary clarity. Ablation experiments and comparative experiments were conducted to evaluate the effectiveness of each component and the performance of the proposed model. RESULTS: The DSRF algorithm could effectively enhance feature representation of small organs to achieve accurate segmentation of the optic chiasm and optic nerves with an average DSC of 0.837 and an ASSD of 0.351. Ablation experiments further verified the contributions of each component in the DSRF method. CONCLUSIONS The proposed deep learning segmentation algorithm can effectively enhance feature representation to achieve accurate segmentation of the optic chiasm and optic nerves in CT images of NPC.
Humans ; Tomography, X-Ray Computed/methods* ; Optic Chiasm/diagnostic imaging* ; Optic Nerve/diagnostic imaging* ; Algorithms ; Nasopharyngeal Carcinoma ; Deep Learning ; Nasopharyngeal Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods*

ObjectiveTo investigate the prognostic differences between primary biliary cholangitis （PBC） patients positive for different autoantibodies and the risk factors for poor prognosis， and to facilitate early and effective intervention for PBC patients. MethodsA total of 141 patients who were diagnosed with PBC for the first time in Fenyang Hospital of Shanxi Province from January 2018 to December 2023 were enrolled and divided into group A （80 patients positive for anti-mitochondrial antibody M2 ［AMA-M2］ alone）， group B （36 patients positive for AMA-M2 and anti-gp210 antibody）， and group C （25 patients positive for AMA-M2 and anti-sp100 antibody）， and the three groups were compared in terms of general information， laboratory markers， and prognosis. The Globe score was used for prognostic evaluation， and a Globe score of<0.3 and the absence of liver cirrhosis at the time of confirmed diagnosis were defined as good prognosis， while a Globe score of ≥0.3 or the presence of liver cirrhosis at the time of confirmed diagnosis were defined as poor prognosis. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s multiple test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for the prognosis of PBC patients； the receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC） was calculated. ResultsCompared with group A， groups B and C had a significantly higher proportion of male patients， a significantly higher detection rate of liver cirrhosis， significantly higher levels of ALT， TBil， and ALP， and significantly lower levels of PLT and Alb （all P<0.05）. The Globe score was calculated based on related indicators after treatment with ursodeoxycholic acid （UDCA） for 1 year， and the results showed that there was a significant difference in prognosis between the three groups （P<0.001）， and compared with group A， groups B and C had a significantly higher proportion of patients with a Globe score of ≥0.3 （P<0.05） and a significantly higher rate of suboptimal response to UDCA （P<0.05）. The univariate Logistic regression analysis showed that anti-gp210 antibody， anti-sp100 antibody， UDCA response， PLT， Alb， ALT， TBil， and ALP were associated with the prognosis of PBC patients （all P<0.05）. The variables meeting related conditions were included in the multivariate Logistic regression analysis， and the results showed that anti-gp210 antibody （odds ratio ［OR］=4.959， 95% confidence interval ［CI］： 1.112 — 22.122， P=0.036）， anti-sp100 antibody （OR=21.666， 95%CI： 1.542 — 304.449， P=0.023）， Alb （OR=0.899， 95%CI： 0.814 — 0.994， P=0.038）， PLT （OR=0.974， 95%CI： 0.963 — 0.985， P<0.001）， and UDCA response （OR=10.275， 95%CI： 1.047 — 100.831， P=0.046） were independent influencing factors for the prognosis of PBC patients. The ROC curve analysis showed that PLT had the best performance in predicting the prognosis of PBC patients， with an AUC of 0.824， a sensitivity of 85.7%， and a specificity of 71.7%. ConclusionPatients with dual positivity for AMA-M2 and anti-gp210 antibody， as well as those with dual positivity for AMA-M2 and anti-sp100 antibody， tend to have a poorer prognosis and a higher rate of suboptimal response to UDCA. Furthermore， positivity for anti-gp210 antibody， positivity for anti-sp100 antibody， thrombocytopenia， hypoalbuminemia， and suboptimal response to UDCA all indicate poor clinical prognosis.

Objective:To understand the baseline viral load (VL) of newly reported HIV- infected patients before antiretroviral therapy and related factors in Tianjin.Methods:Data were obtained from the China Disease Control and Prevention Information System, and the study subjects were HIV-infected patients before the first antiretroviral therapy in Tianjin from 2019 to 2022, and the information about their socio-demographic characteristics, baseline CD4 +T lymphocyte (CD4) counts before antiretroviral therapy and baseline VL test results were collected, the baseline high VL was defined as ≥100 000 copies/ml. The effect of different factors on viral load were analyzed. Software SPSS 24.0 was used for statistical analysis. Results:A total of 1 296 newly reported HIV-infected patients were included in the study, in whom 15.89% (206/1 296) had high baseline VL, and multifactorial logistic regression analysis showed that those with history of STD (a OR=1.45, 95% CI:1.00-2.08) were more likely to have high baseline VL. Compared with those with baseline CD4 counts <200 cells/μl, those with baseline CD4 counts 200-350 cells/μl (a OR=0.40, 95% CI: 0.27-0.57), 351-500 cells/μl (a OR=0.32, 95% CI: 0.20-0.49), and >500 cells/μl (a OR=0.30, 95% CI: 0.18-0.49) were less likely to have high baseline VL. Conclusions:The proportion of HIV-infected patients with high baseline VL before antiretroviral therapy was low in Tianjin during 2019-2022. History of STD and baseline CD4 counts <200 cells/μl were associated with high baseline VL in HIV-infected patients, to which close attention needs to be paid in AIDS prevention and control.

[Objective] To understand the characteristics of dietary diversity of urban families in Ningbo city and analyze the related factors of dietary diversity level. [Methods] The project was carried out based on the baseline survey project of the primary health comprehensive experimental area of the National Health Commission in 2021. Multi-stage stratified cluster random sampling was adopted and household face-to-face inquiry was conducted. The survey questionnaire was divided into four parts: basic information, dietary knowledge and attitudes, dietary consumption frequency, and 24-hour dietary intake. The generalized estimating equation was used to analyze the influencing factors of dietary diversity score. [Results] A total of 632 people were surveyed. Among the nine groups of food (except cooking oils), foods consumed weekly in frequency from high to low were cereals, vegetables, fruits, fish, meat, eggs, beans, and dairy. The overall dietary diversity score (DDS) was 5.78±1.693. Among the surveyed, 9% had insufficient DDS, 62.2% had moderate DDS, and 28.8% had adequate DDS. Age, dietary knowledge acquisition attitude behavior, and family role were significantly correlated with DDS. DDS was 0.70 higher in the group under 40 years old than in the group over 60 years old (P<0.05), and DDS in the group between 40 and 59 years old was 0.46 higher than that in the group over 60 years old (P<0.05). DDS in the occasionally or never actively collected group was 0.93 lower than that in the frequently actively collected group (P<0.001). Among the family role factors, DDS of ordinary family members was 0.32 higher than that of family opinion leader (P<0.05). [Conclusion] The dietary patterns in this region have the characteristics of plant-based and coastal characteristic dietary ones. The intake level of fruits and fish is relatively good, while the intake of legumes and dairy is relatively low, which needs attention.

The pathogens were isolated and purified from the stomach,jejunum and rectum tissues of a Yunnan snub-nosed monkey who died of vomiting,oral and nasal chyme,and abdominal dis-tension,and the species and biological characteristics of the pathogens were studied by biochemical identification,PCR identification,drug susceptibility test,pathogenicity test,serotype identifica-tion,and drug resistance gene and virulence gene analysis.The results showed that the pathogens i-solated from stomach,jejunum and rectum were Escherichia coli(E.coli)serotype O127,belong-ing to enteropathogenic E.coli.They were resistant to cefoxitin and sensitive to gentamicin,gati-floxacin and ciprofloxacin.All the three strains carried drug resistance genes blaTEM and blaCTX-M and virulence genes opmA and opmC.This study provides reference and data support for the prevention and control of enteritis caused by E.coli in Yunnan snub-nosed monkey.

Intracranial seminoma is a rare malignant tumor originating from the germ cells,usually occurring in the pineal gland or pituitary gland.In June 2020,the Department of Endocrinology at the First Affiliated Hospital of Army Military Medical University admitted a 20-year-old male patient with an intracranial germ cell tumor and spinal metastases.The patient presented with headache,dizziness,and visual impairment.Enhanced magnetic resonance imaging(MRI)of the head indicated thickening of the pituitary stalk.After multidisciplinary consultation,the patient underwent endonasal transsphenoidal resection of the tumor,with the pathological diagnosis confirming germ cell tumor.The patient received regular radiotherapy postoperatively.One year later,the tumor recurred and metastasized,leading to a second surgery for tumor resection in the thoracic spinal canal,followed by continued chemotherapy.The patient's clinical symptoms,such as headache and visual disturbances,improved,but he continued to experience panhypopituitarism and required long-term hormone replacement therapy.Early diagnosis of intracranial germ cell tumors is challenging,and they are prone to metastasis and highly sensitive to radiotherapy and chemotherapy.Early diagnosis and multidisciplinary comprehensive treatment can help improve the quality of life and prognosis for patients.

Objective: To understand characteristics of men who have sex with men (MSM) who applied for HIV antibody self-testing reagents through "AIDS self-testing" column of a WeChat official account named "Dark Blue Public Health Center" in Tianjin City, so as to provide insights into exploring online modes of HIV antibody self-testing for MSM. Methods: Data of MSM who were 18 years old or above, currently lived in Tianjin City, had sex with men in the past six months and applied for HIV antibody self-testing reagents through "AIDS self-testing" column from May 2018 to December 2022 were collected. Demographic characteristics, results return and positive findings were descriptively analyzed. Results: Data of 2 064 MSM were collected, including 1 052 MSM aged 20 to 29 years (50.97%), 1 522 unmarried MSM (73.74%), 545 workers (26.41%), 1 385 MSM with college education or above (67.10%), and 315 MSM without testing for HIV antibody in the past (15.26%). A total of 6 470 self-testing reagents were applied, and 5 942 testing results were returned, with a return rate of 91.84%. There were 33.28% (687/2 064) of the applicants applying for 66.32% (4 291/6 470) reagents multiple times. There were 73 MSM with positive results, accounting for 1.23%. Conclusions The MSM applying for HIV antibody self-testing reagents through "AIDS self-testing" are mainly young and highly educated, including some who have never tested for HIV. However, attention should be paid to duplicate applications and the return rate should be increased.

Background: and Purpose Performing the differential diagnosis of Parkinson’s disease (PD) and multiple-system atrophy of parkinsonian type (MSA-P) is challenging. The oculomotor performances of patients with PD and MSA-P were investigated to explore their potential role as a biomarker for this differentiation. Methods: Reflexive saccades and smooth pursuit were examined in 56 patients with PD and 34 with MSA-P in the off-medication state. Results: Patients with PD and MSA-P had similar oculomotor abnormalities of prolonged and hypometric reflexive saccades. The incidence rates of decreased reflexive saccadic velocity and saccadic smooth pursuit were significantly higher in MSA-P than in PD (p<0.05 for both). Multiple logistic regression analysis indicated that slowed reflexive saccades (odds ratio [OR]=8.14, 95% confidence interval [CI]=1.45–45.5) and saccadic smooth pursuit (OR=5.27, 95% CI=1.24–22.43) were significantly related to MSA-P. Conclusions The distinctive oculomotor abnormalities of saccadic smooth pursuit and slowed reflexive saccades in MSA-P may serve as useful biomarkers for discriminating MSA-P from PD.